This research program will develop a broad class of active substrates for mechanistic studies in cell biology and applications in tissue engineering. Most mammalian cells are adherent and must remain attached to the protein extracellular matrix in order to survive, proliferate, differentiate and function. The interactions of cells with the protein matrix are mediated by a host of cell-surface receptors and matrix-derived ligands, which serve not only to localize cells in tissue but also to provide cells with regulatory cues. In many instances, the cues are dynamically modulated: that is, the composition of ligands presented from the matrix changes over time. Experimental studies of dynamic interactions between cell and matrix are difficult and still in need of new tools that can mimic the complex patterns of interactions that are central to cellular regulation. This research program will develop a strategy for creating dynamic substrates wherein the activities of immobilized ligands can be switched in real-time under an electrical control. The program will develop model substrates wherein: i) the activities of ligands can be switched on; ii) the activities of ligands can be switched off; iii) the activities of ligands can be reversibly switched between high and low affinity states. The program will also develop multifunctional substrates that incorporate two or more of these properties. The program will apply these active substrates to a set of model problems in cell biology and tissue engineering in order to validate these strategies and meet the program goals of advancing an approach that will be valuable to experimental studies in cell biology and technologies for engineering tissue. Finally, the program will develop strategies for transitioning these active substrates to users in the biological and bioengineering communities. Classes of substrates that can be modified with a variety of ligands and that incorporate the chemistries for dynamic control over ligand activity will be developed and validated for use. This program will advance a technology that will have broad impact across several areas in biology and medicine.